(a) Field of the Invention
The invention relates to a novel LTB4 agent pharmaceutical formulation of an alkaline pH effective to stabilize the LTB4 agent and provide a formulation with an increased shelf-life. Thus, the invention relates to a composition comprising an LTB4 agent and a pharmaceutically acceptable carrier at an alkaline pH.
(b) Description of Prior Art
Leukotriene B4, itself, is a twenty carbon tetraunsaturated fatty acid and is a relatively unstable molecule. Isotonic aqueous solutions of LTB4 at pH 7.0-7.6, which are suitable for administration to humans and animals are stable for only short periods of time (weeks to months) when stored at temperatures ranging from 2° C. to 25° C. (and above 25° C.). Indeed, LTB4 agents are subject to oxidation, isomerization of double bounds (LTB4 contains two cis and two trans double bounds), racemization (LTB4 contains two chiral centers), esterification (LTB4 contains a carboxylic group), lactonization, among various possible structural alterations.
Although LTB4 agents have a great pharmaceutical utility, their use as therapeutic agents in animals or human is problematic, because of their insufficient stability and shelf-life in solution at temperatures between 2° C. to 25° C.
The scientific literature indicates that until presently, LTB4 formulations for administration to humans and animals are aqueous solutions at pH 7.0-7.5 which are stored at very low temperatures (−20° C. or below) to avoid degradation. Alternatively, LTB4 is used as ethanolic solutions, also stored at low temperature to avoid degradation, which are diluted with a (pH 7.0-7.5) buffer or evaporated to dryness and redissolved in a (pH 7.0-7.5) buffer immediately prior to use. Such formulations are inadequate for the use of LTB4 as a therapeutic agent in humans and animals (unpractical and short shelf-life).
Given the potential of LTB4 agents as a therapeutic agents for the prophylaxis and treatment of infections and cancer in humans and animals, it would be highly desirable to provide with a novel LTB4 agent pharmaceutical formulation of an alkaline pH effective to stabilize the LTB4 agent and provide a formulation with an increased shelf-life.